Emerging therapies that reach the brain could help address the overlooked cognitive and emotional symptoms of Duchenne muscular dystrophy (DMD), offering hope for more complete care, according to a review published recently in the Journal of Neuromuscular Disease.
While DMD is widely known as a muscle-wasting disease, it also affects the brain, with up to half of patients experiencing issues such as learning disabilities, attention problems, anxiety and autism-like behaviors. These symptoms have long been recognized but remain largely untreated.
The condition results from mutations in the dystrophin gene, which not only plays an important role in muscles but in the brain, as well. The more versions — or isoforms — of dystrophin that are missing, the more likely a child is to face intellectual and emotional challenges. Research shows children missing all three major isoforms (Dp427, Dp140 and Dp71) are far more likely to experience severe neurodevelopmental symptoms compared to those missing just one.
Animal studies using mice with the same mutations as humans have helped scientists understand how the absence of dystrophin affects brain function. These mice show problems with memory and learning and high levels of fear and anxiety. Scientists have traced these symptoms to problems with how certain brain chemicals work, including changes in GABA signaling, which helps regulate mood and behavior.
Read more about DMD signs and symptoms
Traditional DMD treatments such as exon-skipping therapies have focused only on muscle symptoms, because these treatments cannot cross the blood-brain barrier. However, new delivery methods, including injecting antisense oligonucleotides into the fluid around the brain or using modified antisense oligonucleotides that can reach the brain, have shown early promise. In mice, these methods led to partial dystrophin restoration and behavioral improvements.
“Although challenges remain — ranging from improving targeting precision to ensuring long-term safety — these advancements bring hope,” explained the authors of this review. “With sustained research efforts, the prospect of treating both peripheral and CNS symptoms of MDs [muscular dystrophies] may soon become a reality, offering patients a significantly improved quality of life.”
Despite this progress, challenges remain. Many of these therapies restore only small amounts of protein in the brain, and some require repeated procedures. Side effects, such as kidney concerns, have also been reported in early human trials for next-generation antisense oligonucleotides.
Still, these advances suggest that future treatments could eventually target both the muscles and brain in DMD. For families affected by Duchenne, that could mean not just stronger bodies but also clearer thinking, improved learning and better emotional health.
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